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September 2018. RNA chaperones form a sequentially and structurally diverse class of proteins and are important for promoting many RNA-regulated cellular processes. One prime example is the ribosomal protein S1 (rS1). Initiation of the translation of bacterial genes into proteins requires that the ribosome-binding site in messenger RNAs (mRNAs) adopts single-stranded conformations. In Gram-negative bacteria rS1 is a key player in resolving structured elements in mRNAs. However, the exact mechanism of how rS1 unfolds persistent secondary structures in the translation initiation region remained unknown.

A study conductedby a team of scientists at Goethe University Frankfurt now provides important insights into how rS1 exploits its modular domain architecture to enable translation of structured RNAs by locally melting RNA secondary structure.

The scientists investigated the rS1 of the pathogenic bacterium Vibrio vulnificus and found that it displays a unique architecture of mRNA-binding domains, where domains D3 and D4 provide the mRNA-binding platform and cover the nucleotide binding length of the full-length rS1. D5 significantly increases rS1’s chaperone activity, although it displays structural heterogeneity both in isolation and in presence of the other domains, albeit to varying degrees. The heterogeneity is induced by the switch between the two equilibrium conformations and is triggered by an order-to-order transition of two mutually exclusive secondary structures (β-strand-to-α-helix) of the ‘AERERI’ sequence. The conformational switching is exploited for the melting of structured 5′-UTR’s, as the conformational heterogeneity of D5 can compensate the entropic penalty of complex formation.

These new data provide a detailed understanding of the intricate coupling of protein and RNA folding dynamics that enable translation initiation of structured mRNAs. More ...